Genetic Variant NM_020183.6:c.484+30A>G (chr12-27380434-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020183.6(BMAL2):c.484+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,609,668 control chromosomes in the GnomAD database, including 262,463 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 20646 hom., cov: 31)

Exomes 𝑓: 0.57 ( 241817 hom. )

Consequence

BMAL2
NM_020183.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.907

Publications

13 publications found

Variant links:

Genes affected

BMAL2 (HGNC:18984): (basic helix-loop-helix ARNT like 2) This gene encodes a basic helix-loop-helix transcription factor belonging to the PAS (PER, ARNT, SIM) superfamily. The PAS proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. This protein forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. Consistent with its role as a biologically relevant partner of circadian and hypoxia factors, this protein is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

BMAL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL2	NM_020183.6 link	c.484+30A>G		intron_variant	Intron 5 of 16	ENST00000266503.10	NP_064568.3	Q8WYA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10 link	c.484+30A>G		intron_variant	Intron 5 of 16	1	NM_020183.6	ENSP00000266503.5		Q8WYA1-1
BMAL2	ENST00000457040.6 link	c.337+30A>G		intron_variant	Intron 3 of 14	1		ENSP00000400185.2		H0Y5R1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74491

AN:

151862

Hom.:

20633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.541

GnomAD2 exomes

AF:

0.562

AC:

140383

AN:

249836

AF XY:

0.561

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.752

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.569

AC:

829478

AN:

1457688

Hom.:

241817

Cov.:

AF XY:

0.568

AC XY:

411470

AN XY:

725022

show subpopulations

African (AFR)

AF:

0.214

AC:

7133

AN:

33392

American (AMR)

AF:

0.743

AC:

33143

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

18305

AN:

26008

East Asian (EAS)

AF:

0.297

AC:

11779

AN:

39630

South Asian (SAS)

AF:

0.474

AC:

40696

AN:

85876

European-Finnish (FIN)

AF:

0.572

AC:

30526

AN:

53322

Middle Eastern (MID)

AF:

0.589

AC:

3390

AN:

5752

European-Non Finnish (NFE)

AF:

0.587

AC:

651344

AN:

1108908

Other (OTH)

AF:

0.551

AC:

33162

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

16347

32693

49040

65386

81733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.490

AC:

74527

AN:

151980

Hom.:

20646

Cov.:

AF XY:

0.492

AC XY:

36569

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.226

AC:

9376

AN:

41462

American (AMR)

AF:

0.682

AC:

10428

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.696

AC:

2416

AN:

3470

East Asian (EAS)

AF:

0.320

AC:

1648

AN:

5146

South Asian (SAS)

AF:

0.462

AC:

2221

AN:

4806

European-Finnish (FIN)

AF:

0.583

AC:

6159

AN:

10568

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.595

AC:

40406

AN:

67932

Other (OTH)

AF:

0.542

AC:

1143

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1688

3376

5064

6752

8440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.563

Hom.:

77070

Bravo

AF:

0.487

Asia WGS

AF:

0.370

AC:

1288

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.74

(source)

DANN

Benign

0.21

PhyloP100

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_020183.6:c.484+30A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over